Abstract: Provided herein are chimeric minigenes, where the alternative splicing of the minigene determines whether an encoded gene is expressed. In particular, the minigenes are alternatively spliced in response to splicing modulator dmgs, such that the encoded gene is only expressed in the present of the splicing modulator dmg. The encoded gene may encode an inhibitory RNA, a CRISPR-Cas9 protein, a transactivator, or a therapeutic protein.

Abstract: Compositions and methods are provided for the inhibition, treatment and/or prevention of Huntington's disease and related disorders.

Abstract: Compositions and methods are provided for the inhibition, treatment and/or prevention of Huntington's disease and related disorders.

Abstract: Provided herein are nucleic acids that comprise both an expression cassette for a therapeutic protein (e.g., Ataxin-1-like) and an expression cassette for a therapeutic inhibitory RNA (e.g., a miRNA that targets ataxin-1 mRNA). In some instances, the expression cassette for the therapeutic inhibitor RNA lies within an intron of the expression cassette for the therapeutic protein. Also provided are methods of using the nucleic acids to treat spinocerebellar.

Abstract: CRISPR/Cas9-mediated genome editing holds clinical potential for treating genetic diseases, such as spinocerebellar ataxia type 2, which is caused by mutations in the ATXN2 gene. Here, compositions and methods for the treatment of spinocerebellar taxia type 2 are provided. In some embodiments, a composition providing a vector encoding a guide RNA of the disclosure and a vector encoding a Cas9 protein or nuclease domain thereof of the disclosure are provided for use in the treatment of spinocerebellar ataxia type 2.

Abstract: Provided herein are chimeric transactivator minigenes, where the alternative splicing of the minigene determines whether a transactivator is expressed. Expression of the transactivator results in the transcription of a target gene that is under the control of a designer promoter sequence. Alternatively, provided herein are chimeric target gene minigenes, wherein the alternative splicing of the minigene directly determines whether the target gene is expressed. The target gene may encode an inhibitory RNA, a CRISPR-Cas9 protein, or a therapeutic protein.

Abstract: The present disclosure provides filler or stuffer sequences, compositions thereof including expression cassettes and vectors, such as viral (e.g., AAV) vectors and methods of delivering a therapeutic agent to a mammal and/or treating a disease.

Abstract: The invention provides expression cassettes and vectors, such as viral (e.g., AAV) vectors, comprising a first nucleic acid encoding a nuclease defective Cas 9 (dCas9) polypeptide and a second nucleic acid encoding a guide polynucleotide that targets the dCas9 polypeptide to the transcriptional start site of an allele encoding a mutant huntingtin gene (HTT)-encoded protein. Also provided are pharmaceutical composition comprising the disclosed expression cassettes and vectors, as well as methods of inhibiting expression of a mutant HTT protein and of treating Huntington's Disease and symptoms associated with the disease.

Abstract: The present disclosure provides filler or stuffer sequences, compositions thereof including expression cassettes and vectors, such as viral (e.g., AAV) vectors and methods of delivering a therapeutic agent to a mammal and/or treating a disease.

Abstract: Compositions and methods are provided for the inhibition, treatment and/or prevention of Huntington's disease and related disorders.

Abstract: An isolated promoter sequence comprising a nucleic acid of between 600 and 1700 nucleotides in length having at least 90% identity to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7.

Abstract: The present invention is directed to RNA interference (RNAi) molecules targeted against a nucleic acid sequence, and methods of using these RNAi molecules to reduce off-target toxicity.

Abstract: The present invention is directed to RNA interference (RNAi) molecules targeted against a nucleic acid sequence, and methods of using these RNAi molecules to reduce off-target toxicity.

Abstract: An adeno-associated virus filler component comprising a nucleic acid of between 3300 and 4200 nucleotides in length is disclosed.

Abstract: The present invention is directed to RNA interference (RNAi) molecules targeted against a nucleic acid sequence, and methods of using these RNAi molecules to reduce off-target toxicity.

Abstract: The present invention is directed to RNA interference (RNAi) molecules targeted against a nucleic acid sequence, and methods of using these RNAi molecules to reduce off-target toxicity.

Abstract: An adeno-associated virus filler component comprising a nucleic acid of between 3300 and 4200 nucleotides in length is disclosed.

Abstract: The present invention is directed to RNA interference (RNAi) molecules targeted against a Huntington's disease nucleic acid sequence, and methods of using these RNAi molecules to treat Huntington's disease.

Abstract: The present invention is directed to RNA interference (RNAi) molecules targeted against a nucleic acid sequence that encodes poly-glutamine repeat diseases, and methods of using these RNAi molecules.

Abstract: The present invention is directed to RNA interference (RNAi) molecules targeted against a Huntington's disease nucleic acid sequence, and methods of using these RNAi molecules to treat Huntington's disease.